Cancer is a complex and adaptable disease, and knowledge of the mechanisms that cause its progression is vital to creating and monitoring anti-cancer therapies. As a tumor grows beyond a few mm3, blood vessels are recruited to provide additional nutrients in a process called angiogenesis. Some novel drug therapies specifically target this process, and the efficacy of these drugs can in principle be monitored by a technique called angiography. 3D angiography, a method of imaging the vasculature, can be performed by several imaging modalities typically with the use of a contrast agent.
A technique is introduced which uses high resolution ultrasound in conjunction with an ultrasound contrast agent to produce 3D images of the vasculature. This method offers a faster, more accessible, and cheaper alternative to assess the efficacy of anti-angiogenic drugs in preclinical cancer models. In addition to vessel imaging, modeling the kinetic behavior of the contrast agent in the vasculature can elucidate parameters such as blood flow, which can also serve as an indicator of drug treatment efficacy. The repeatability of a commonly used mono-exponential model is assessed in order to determine thresholds for inter/intra-subject error.
The 3D vessel imaging technique presented in this thesis correlated with other measures of blood flow (r = 0.55 ± 0.04, p < 0.01) and shows an increased sensitivity to microvasculature within tumors. Also, preliminary repeatability analysis (n = 6) on the modeling parameter which is proportional to contrast agent velocity shows a mean difference of 0.061 ± 0.298 between independent measurements, and the limits of agreement range from -0.536 and 0.656. The developments exhibited provide additional methods for monitoring longitudinal anti-angiogenic cancer treatments in preclinical models.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12072007-103700 |
| Date | 27 December 2007 |
| Creators | Loveless, Mary Elizabeth |
| Contributors | Dr. Thomas E. Yankeelov, Dr. John C. Gore |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12072007-103700/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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